1. The Field of the Invention
The present invention is directed generally to a surface construction applicable to a temporary implantation of medical devices in vivo and more particularly to an intravascular catheter having surface qualities capable of preventing the formation of biofilm.
2. Background Art
Many solutions have been attempted in combating infections caused by intravascularly implanted medical devices or catheters. The treatment of entry sites of percutaneously implanted devices have dramatically reduced infections caused by the transfer of microbes from the surface tissue or skin of a person or animal to the intravascular, organ or body tissue infections. However, infections due to microbes already present within the body remain serious cause of infections and ill health. Common solutions include but not limited to coating of surfaces with anti-microbial drugs, modification of surface charges, implementation of ultrasonic vibrating devices, etc. However, such solutions may cause negative side effects such as in the case of anti-microbial drugs. Modification of surface charges and implementation of ultrasonic vibrating devices require complicated equipment which not only increase costs but also require constant or periodic power use, sophisticated control and actuating devices.
U.S. Pat. No. 7,947,301 to Bischoff et al. discloses anti-infective articles capable of preventing infection associated with implantation of medical devices include low levels of anti-infective agents, may cover only a fraction of the portion of the medical device and be effective, or may rapidly elute anti-infective agent, without sustained elution. This patent further discloses the use of minocycline and rifampin which can cause negative effects. Minocycline has been known to cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, mouth sores, headache and vomiting. Rifampin on the other hand has been known to cause diarrhea, dizziness, drowsiness, gas, headache, heartburn, menstrual changes, mild upset stomach and cramps. As the anti-infection effectiveness of the articles depend on the elution of a drug, various factors such as the size, shape, surface exposure area of the drug used and the environment in the which the articles are disposed and the like can affect the elution rate of the drug. Therefore the elution rate and hence the period of which a drug remains effective can hardly be ascertained.
U.S. Pat. Pub. No. 2011/0098323 discloses an organic compound for combating Gram-positive biofilm-forming bacteria. Timed release of such compound is also problematic as it also depends on its in-situ elution which may not be accurately controlled. In addition, the formulation of such compound involves numerous active compounds which translate to higher materials and manufacturing costs.
U.S. Pat. No. 7,820,284 to Terry discloses microbe-resistant medical devices and methods of making these medical devices. A base coat is applied to at least a portion of a surface of a device. The base coat includes one or more types of antimicrobial particles that are held in the base coat. A polymeric over coat is applied over at least a portion of the base coat. The over coat may be an organic soluble polymer, a water soluble polymer, a hydrogel or any other polymer capable of being coated onto a medical device. The polymer of the over coat is dissolvable in a solvent that does not dissolve the polymeric base coat during application of the over coat. The over coat remains free of the antimicrobial particles by not dissolving the base coat during the over coating process. This patent teaches a process for applying a multi-layer lubricious coating including antimicrobial particles to surfaces of a medical device.
U.S. Pat. No. 7,393,501 to Zumeris et al. discloses an apparatus, system and method for preventing or treating biofilm associated with catheters. A piezo-ceramic element is attached to a catheter, and a vibration processor is connected to the piezo-ceramic element. The vibration processor provides electric signals that generate acoustic vibrations in the piezo-ceramic element, causing vibrations in or around the catheter. These vibrations are administered to disperse microbe colonies, thereby preventing or inhibiting formation of biofilm that may lead to infections. Vibrations may be amplified significantly due to resonance conditions in the catheter balloon, which may be powerful enough to be used to disperse microbe colonies that have grouped around the catheter or are attempting to do so. This patent teaches a positively and in-situ powered device which requires external power and its active administration to prevent further infection.
An article entitling “Scanning Electron Microscopy of Surface Irregularities and Thrombogenesis of Polyurethane and Polyethylene Coronary Catheters” by Bourassa et al. (hereinafter Bourassa) of Vol. 53, No. 6, June 1976 of the Journal of the American Heart Association disclosed adherent thrombi on all external surfaces of Ducor polyurerathane and polyetylene catheters. Bourassa went on to summarize their finding as:                “Following routine coronary artriography, surface irregularities and thrombogenesis of the inner and outer wall of six Ducor polyurethane and six RPX polyethylene coronary catheters were studied by scanning electron microscopy. Polyurethane catheters had rough and highly irregular external and internal surfaces. All catheters showed adherent thrombi on their external surface. The internal surface of three catheters showed evidence of thrombosis. Polyethylene differed from polyurethane in several respects. Although the external surface had an irregular and wavelike appearance, the internal surface was smooth and regular. Two polyethylene catheters showed thrombi on their external surface. The internal surface of one catheter showed single platelets in one area. These results confirm recent reports showing that internal and external surface irregularities play a major role in the initiation of thrombosis in and on intravascular catheters. They stress the need for high quality catheter materials with smooth and regular surface in the prevention of thromboembolic complications from coronary arteriography.”        
It is evident from the foregoing statement that a smooth and regular surface is thought to be of superior quality in preventing thromboembolic complications. As will be disclose hereinafter, such hypothesis may be problematic and the contrary may be true.
A biofilm is a community of sessile, stably attached microorganisms, especially bacteria, embedded in a hydrated matrix of extracellular polymeric substances exhibiting growth properties that are distinguished from those of planktonic, free-living microorganisms. Biofilms represent a target of new compositions for inhibiting, reducing, preventing, and removing microbial infections, and are believed to be partly responsible for increasing the rates of antibiotic resistance. It is thought that upwards of 60% of all nosocomial (hospital-derived) infections are due to biofilms, whose role in contaminating medical implants is now well established. Central venous catheters (CVCs) pose the greatest risk of device-related infections with infection rates of 3 to 5% and account for the most serious and costly healthcare-associated infections (See for example, Donlan and Costerton, Clin. Microbiol. Rev., Vol. 15, No. 2, pp. 167-193, 2002; Davey and O'Toole, Microbiol. Mol. Biol. Rev., Vol. 64, No. 4, pp. 847-867, 2000).
One approach to managing biofilm infections is to identify the microorganism(s) in the biofilm and to find antibiotic or biocidal agents capable of killing the microorganisms. A major limitation of this approach is that models for testing the efficacy of these agents to not sufficiently represent a biofilm environment. Biofilm bacteria can be up to 1.000-fold more resistant to antibiotic treatment than the same organism grown planktonically.
Biofilm bacteria are also more resistant to biocides, such as peroxide, bleach, acids, and other biocidal agents.
In spite of the dramatic differences in susceptibility to antimicrobial agents between planktonic and sessile, biofilm microorganisms, current approaches for targeting biofilm microorganisms are insufficient in addressing this discrepancy. Antimicrobial efficacy testing often employs standard broth microdilution methods reflecting antibiotic efficacy in planktonic, rather than biofilm systems. Accordingly, broad numbers of prospective antibiotic- and biocidal agents have been identified without any expectation of success in the more “real” biofilm world.
The mechanisms by which resistance to antibiotic or biocidal agents is achieved remain subject to speculation. In recent years, biofilm-based infections attributed to medical devices, such as catheters, prosthetic heart valves, contact lenses, and intrauterine devices have received increased attention. Despite circumstantial evidence suggesting biofilm to be a major culprit responsible for chronic wounds, their role in chronic wounds remains poorly understood.
Thus, there arises a need for a catheter which does not rely on the presence and release of antibiotics, biocidal agents or other medicines for combating biofilm formation as the medicine may create negative effects. An antimicrobial-coated catheter relies on the presence of an antimicrobial substance and its regulated release to be effective. As the elution rate of such substance can vary from person to person, close monitoring of the effectiveness of such substance is still required. Further, there arises a need for a catheter that is reliable and effective in combating biofilm formation in all conditions and a catheter which does not require close monitoring and external power to prevent microbe growth.